Bloomberg Businessweek - USA (2019-10-14)

Bloomberg Businessweek October 14, 2019

● Drugmakers are bettingbig

on technologies thattagand

destroy the proteinsbehind

fatal diseases

PHOTO:

GEORGE

ETHEREDGE/BLOOMBERG

19

Using the Body’s

Trash Disposals to

Fight Cancer

Attheirmostbasiclevel,manyofthedeadliestdis-

easesarecausedbynestsofmisguidedproteins.

Mostmedicinesworkbyattachingthemselvesto

theseproteinsandtemporarilyshuttingthemdown.

Inthe1990s,YaleUniversityscientistCraigCrews

anda colleaguehada radicalidea:Whatif a drug

coulddestroya badproteinbymakingit a targetof

thebody’sownmoleculartrashdisposalmachines?

Foryears,theideawasa labcuriosity.Biotech

investorswouldn’tinitiallybacka companybased

ontheconcept,whichCrewsanda fewotheraca-

demicslaboredtoprovecouldbea practicalway

tomakedrugs.Thefieldgota bigboostearlierthis

decadewhenscientistsdiscoveredthatsomeofthe

mostsuccessfulmedicinesturnedouttoworkby

piggybackingontothesehumantrashcollectors.

Nowit’sbecomeoneofthehottesttechnologies

formakingpills.Crewsanda biotechhefounded,

ArvinasInc.,areracingsomeoftheworld’sbiggest

pharmaceuticalandbiotechcompanies—Novartis,

Amgen,and GileadSciences—to turn protein-

degradingcompoundsintodrugs.“Byhijackingnat-

uralquality-control machinery inside cells, we are

literally making problem proteinsgoaway,”hesays.

The new drugs, dubbedproteindegraders,

could be among the most significantadvancesin

drugmaking technology in decades.Unlikespe-

cialized gene therapies, treatmentsbasedonpro-

teindegraderscouldbemass-producedinpill

form.Therecouldbea rangeofapplications,

fromvanquishingdrug-resistanttumorstoclear-

ing clusters of disease-causingproteinsfromthe

brains of Parkinson’s or Alzheimer’ssufferers.“No

other technology has the potentialtohavesucha

broadimpact,”saysNelloMainolfi,founderand

presidentofKymeraTherapeutics,a biotechthat

attracted$70millioninfundinginMayfromVertex

PharmaceuticalsInc.touseproteindegraders to

tackle undisclosed specialty diseases.

What’s perhaps most intriguing to drug scien-

tists is that degraders could help researchers target

thousands of proteins now considered “undrugga-

ble,” including several linked to common cancers.

“This set of technologiesis rapidlyadvancing,”says

Robert Bradway, chiefexecutiveofficerofAmgen

Inc. “It will enable ustoreconceive the druggable

Edited by

Rebecca Penty and

Jeff Muskus

Crews pioneered

protein degrader

drug technology

T E C H N O L O G Y

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